Our heritage in helping develop medicines that have a global impact is long and in the antiviral space includes the marketed drug ISENTRESS®, for HIV, and Grazoprevir, a component of HCV ZEPATIER® combination therapy.
Extensive work by our Infectious Disease Unit in supporting profound scientific advances, means we have first-hand experience in deploying a full suite of innovative in-house technologies to help companies progress faster in the discovery of small molecules or peptides that can become new standards of care for infectious diseases.
As science advances by collaboration, we work closely with our partners to combat the bane of infectious diseases, including the parasitic – Malaria and Trypanosomiasis as well as the viral – Zika, Dengue and, more recently coronavirus which are all a massive health burden for many countries. For Hepatitis B, we have worked with our partners, to discover a novel series of fourth-generation capsid assembly modulators (CAMs). These partners include the National Consortium and Collection of Chemical Compounds (CNCCS), which is a private-public consortium with a mission to be a ‘Lead Factory’, identifying compounds which are active against innovative biological targets. The CNCCS also functions as a centre for translational research in rare, neglected and poverty-related diseases. For coronavirus, IRBM is collaborating with Merck & Co to identify and develop novel peptide therapeutics active against different strains of coronavirus, including SARS-CoV-2.
We have leveraged sophisticated molecular and cellular biology techniques to develop in-house replication assays for many viruses and parasites, and including the recently established, robust SARS-COV-2 replication assay highly suitable for drug discovery. These rapid, high throughput, luminescence assays, provide a powerful way to assess the potential of viral-suppression candidate therapeutics. In addition to assay development, we can contribute significantly to the target validation processes and to mechanism of action determination through, when possible, the generation of resistant mutants and reverse genetics.
We are passionate about working together to protect the most vulnerable populations worldwide and help ease human suffering. The intent is to help ensure a more resilient global response to future epidemics by producing new potential treatments from well validated targets.
If you are passionate like us to make a difference in infectious diseases, then get in touch.
We cover the broad range of drug discovery phases from target validation through to candidate nomination for both small molecules and peptides. In the tables below we provide a selection of the types of assays we can apply to your program and the sub genomic replicons we have developed for specific antiviral diseases.
IN VITRO BIOLOGY ASSAYS TO SUPPORT INFECTIOUS DISEASE PROGRAMS
Biochemical and cell-based assays
High throughput screening
High-content microscopy and phenotypic screening
REPLICONS TO ASSESS EFFICACY AND BIOAVAIABILITY OF DRUG CANDIDATES
|Stable replicon||Transient Replicon|
|HCV (in Huh 7.5)||SARS-CoV-2|
|Zika (in Vero and Huh 7.5)|
|Dengue (in Vero)|
|Chikungunya (in Vero)|
Infectious disease publications
- Ferrigno, F., Biancofiore, I., Malancona, S., Ponzi, S., Paonessa, G., Graziani, R., Bresciani, A., Gennari, N., Di Marco, A., Kaiser, M., Summa, V., Harper, S. and Ontoria, J.M.. (2018) Discovery of 2-(1H-imidazo-2-yl) piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro. Bioorg Med Chem Lett.; 28(23-24), 3689-3692.
- Ponzi, S., Bresciani, A., Kaiser, M., Nardi, V., , Nizia, E., Ontoria, J.M., Pace, P., Paonessa, G., Summa, V., and Harper, S.. (2020) Discovery of 4-((1-(1H-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of Trypanosoma cruzi growth inhibitors. Bioorg Med Chem Lett.; 30(8), 127052.
- Colarusso, S., Ferrigno, F., Ponzi, S., Pavone, F., Conte, I., Abate, L., Beghetto, E., Missineo, A., Amaudrut, J., Bresciani, A., Paonessa, G., Tomei, L., Montalbetti, C., Bianchi, E., Toniatti, C., Ontoria,J.M.. (2022) SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease. Bioorganic and Medicinal Chemistry, 57, 116631.
- Paonessa, G., Siciliano, G., Graziani, R., Lalli, C., Cecchetti, O., Alli, C., La Valle, R., Petrocchi, A., Sferrazza, A., Bisbocci, M., Falchi, M., Toniatti, C., Bresciani, A., Alano, P.. (2022) Novel gametocyte-specific and all-blood-stage transmission-blocking chemotypes from high throughput screening on Plasmodium falciparum gametocytes. Communication Biology, Jun 6;5(1):547.